Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Biomedical Engineering Research Center, Faculty of Engineering, Chulalongkorn University, Bangkok, 10330, Thailand.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Pharm Sci. 2024 Mar;113(3):718-724. doi: 10.1016/j.xphs.2023.09.001. Epub 2023 Sep 9.
Triggerable coatings, such as pH-responsive polymethacrylate copolymers, can be used to protect the active pharmaceutical ingredients contained within oral solid dosage forms from the acidic gastric environment and to facilitate drug delivery directly to the intestine. However, gastrointestinal pH can be highly variable, which can reduce delivery efficiency when using pH-responsive drug delivery technologies. We hypothesized that biomaterials susceptible to proteolysis could be used in combination with other triggerable polymers to develop novel enteric coatings. Bioinformatic analysis suggested that silk fibroin is selectively degradable by enzymes in the small intestine, including chymotrypsin, but resilient to gastric pepsin. Based on the analysis, we developed a silk fibroin-polymethacrylate copolymer coating for oral dosage forms. In vitro and in vivo studies demonstrated that capsules coated with this novel silk fibroin formulation enable pancreatin-dependent drug release. We believe that this novel formulation and extensions thereof have the potential to produce more effective and personalized oral drug delivery systems for vulnerable populations including patients that have impaired and highly variable intestinal physiology.
可触发涂层,如 pH 响应性聚甲基丙烯酸酯共聚物,可用于保护口服固体制剂中含有的活性药物成分免受酸性胃环境的影响,并促进药物直接递送至肠道。然而,胃肠道 pH 值可能高度可变,这会降低使用 pH 响应性药物递送技术的递送效率。我们假设,易受蛋白水解的生物材料可以与其他可触发聚合物结合使用,以开发新型肠溶涂层。生物信息学分析表明,丝素纤维蛋白可被包括胰凝乳蛋白酶在内的小肠内的酶选择性降解,但能抵抗胃蛋白酶。基于该分析,我们为口服剂型开发了一种丝素纤维蛋白-聚甲基丙烯酸酯共聚物涂层。体外和体内研究表明,用这种新型丝素制剂包衣的胶囊能够实现依赖于胰酶的药物释放。我们相信,这种新型制剂及其延伸制剂有可能为包括肠道生理功能受损和高度可变的患者在内的脆弱人群生产更有效和个性化的口服药物递送系统。